Efficacy and safety of cladrabine in LCH

1. Efficacy and Safety of Cladribine as salvage therapy in patients with
relapsed/refractory Langerhans Cell Histiocytosis
: A single-center study of thirteen cases
Authers:
Dr. Ajay Yadav,
Dept. of Medical Oncology, AIIMS, New Delhi

2. Introduction
• LCH is a heterogonous disease which can affect any organ or system of
the body
• Clinical course varies from a self limiting disease to a rapidly
progressive fatal disease
• Clinical manifestations depend on site & extent of organ involvement
• Response to chemotherapy is very good but some patients develop
recurrence after first line treatment

3. Introduction
Localized Disease Multi-system disease
Good Prognosis
Require minimal or
no treatment
Poor Prognosis
Require Cytotoxic
agents
Relapsed DsRefractory Ds

4. Methods
• We reviewed the data of recurrent or refractory LCH treated at
our center between March’2006 to March’2014
• Safety and efficacy (response rate & progression-free survival)
were evaluated
• PFS was calculated from the date of progression after 1st line
treatment to the date of progression after salvage therapy with
cladrinbine

5. Results
• N=13
• Median age: 4 years (range: 1-28); Male: Female - 10:3
• All patients received prednisolone, 6-MP, vinblastine and Vp-16
(two patients without etposide) as their 1st line treatment
• Initial response-
– PR-10; SD-1; PD-2
• Median time to progression after 1st line treatment: 16.6 months
(range: 5-30.9)

6. Patient’s characteristics
Case Sex Age at diagnosis (Yrs) Site involved
1
M 1
MULTISYSTEM “RISK”
PATIENTS
Skin, Bone, Liver
2
F 5
MULTISYSTEM “RISK”
PATIENTS
Bone, Lung, Liver
3 M 6 Multisystem Low risk Skin, Bone
4
M 5
MULTISYSTEM “RISK”
PATIENTS
Skin, Bone, CNS, Lung
5 M
3
MULTISYSTEM “RISK”
PATIENTS
Bone, Lung
6
M 2
MULTISYSTEM “RISK”
PATIENTS
Skin, Bone, Liver
7
M 4
MULTISYSTEM “RISK”
PATIENTS
Skin, Bone, Bone marrow
8 M 1 Multisystem Low Risk Skin, Bone
9
M 4
MULTISYSTEM “RISK”
PATIENTS
Skin, Bone, Lung
10 F 2 Multisystem Low risk Skin, Bone
11 M 13 Single System Skin
12 F 1.5 Multisystem Low risk Skin, Bone
13 M 28 Single System Bone

7. Response
Response Number %
Complete response 5 38
Partial response 1 8
Stable disease 2 15
Progressive disease 3 24
Unknown response 2 15
Use: 2nd line-6; 3rd line-7
Overall response rate: 46% (n=6/13)
Disease control rate: 62% (n=8/13)

8. Toxicity & outcome
• Grade ¾ febrile neutropenia: 3
• Pneumonia: 1
• No toxicity related death
• Median follow up: 72 months
– Median PFS: 22 months
– 5-year overall survival was: 92.3%

9. 0.000.250.500.751.00
0 20 40 60 80
Time since progression after 1st line treatment
0.000.250.500.751.00
0 50 100 150
Time since diagnosis
Kaplan-Meier PFS estimate Kaplan-Meier OS estimate
Survivalproportion
Survivalproportion

10. Conclusion
• Cladribine is highly effective with manageable toxicity in
patients with relapse/refractory LCH
• Many patients respond to subsequent line of therapy and had
good overall survival
• Cladribine as salvage therapy can induce a long term disease
control and even cure

11. THANK YOU